The purpose of this project is to assess the feasibility of utilizing a patented nanosphere drug delivery system for ophthalmic use. This system has been demonstrated to have potential in a variety of other applications, including oral and transdermal delivery of drugs such as insulin and estradiol. Although numerous nanoparticle drug delivery systems have been reported in the literature, the nanosphere system presented in this proposal has unique properties, in that it is based on a carbohydrate core, is biodegradable and non-toxic, and is stable in solution. Furthermore, both the shell and the core can be functionalized independently. The functionalizable shell enables the attachment of targeting moieties to the nanospheres without affecting the properties of the core. The structure of the nanospheres and their ability to be functionalized can be utilized for controlled release of the encapsulated drugs, which will take place at the targeted site. One can theoretically encapsulate any type of drug, regardless of structure, enabling the system to be adaptable for any ophthalmic drug in which increased residence time or corneal permeability is desirable. The specific aims of this project are to: 1. Investigate the binding properties of the nanospheres to epithelial carbohydrate-binding sites in a cell culture model, and in excised bovine eyes; and 2. Investigate the release characteristics of 3 structurally and functionally distinct ophthalmic drugs encapsulated into nanospheres. During Phase II, the investigation will incorporate animal models for in vivo pharmacokinetic and pharmacodynamic studies, establish the cytotoxic profile of the nanospheres, and standardize synthesis and analytical methods with the ultimate intention of fulfilling requirements for pharmaceutical manufacture of FDA-approved drugs.